A cross sectional entomological study was carried out from January to December 2021 in the district of Parakou, East-Benin in order to evaluate the effects of pyrethroids and carbamates on the immune system of Culex quinquefasciatus. The study was based on assessing the susceptibility of adults of Cx. quinquefasciatus aged 2-5 days from larvae collected in two urban areas (Zongo and Tranza) and in two rural areas (Beyerou and Tourou). These mosquitoes were subjected to insecticide-impregnated papers (bendiocarb 0.1%, deltamethrin 0.05%, permethrin 0.75% and DDT 4%) following WHO testing protocol. The presence of G119S mutation in the acetyl cholinesterase-encoding gene (ace-1) and the knock down resistance (L1014F) were done with the surviving and dead mosquitoes post testing. Moreover, Mixed Function Oxidase (MFO), non-specific esterase (NSE) and glutathione-S-transferases (GST) activity in Cx. quinquefasciatus from each zone were evaluated and compared to the S-Lab (reference strain of Cx. quinquefasciatus). Results from this study shows that Cx. quinquefasciatus populations were fully resistance to DDT (3% as a means of mortality), permethrin (15%), deltamethrin (22%) and bendiocarb (86%). The L1014F mutation was found both in urban and rural areas with 0.85 as mean of frequency. The Ace-1 mutation was found at a very low frequency (≤ 5%). Moreover, Esterase, Glutathione-s-transferase (GST) and P450 monooxygenase activities were significantly higher in the wild population of Cx. quinquefasciatus populations from all the sites compared to the reference strain S-Lab (P < 0,05). These findings showed that insecticide resistance status in Cx. quinquefasciatus in the district of Parakou is alarming. It’s therefore crucial to develop Integrated Pest and Vector Management (IPVM) strategies for better control of this filariasis vector in this district.